Burge:Research: Difference between revisions

==RNA splicing specificity==

Most eukaryotic genes contain one or more introns which must be removed from the primary transcript by the RNA splicing machinery in order to create the proper mRNA sequence to direct protein synthesis. This process must be highly accurate in order to ensure production of adequate amounts of correctly processed mRNA. The problem of RNA splicing specificity is to describe the set of `rules' which govern choice of intron and splice site locations in primary transcripts by the nuclear splicing machinery and to understand the molecular basis for these rules. This problem is analogous to the problem faced by biochemists in the early 1960s of identifying the rules governing translation of mRNAs into specific peptide sequences by the ribosome, the solution of which was the genetic code. The rules governing splicing are likely to be more complicated than those for translation, and are not exactly the same in all organisms. On the other hand, progress in large scale sequencing efforts is providing a wealth of data related to this problem in the form of thousands of gene sequences of known exon-intron structure. A typical human primary transcript is 30 kilobases long and contains about ten exons separated by much larger and more variably sized introns. The discrepancy between human exon and intron lengths led to the "exon definition" model of splicing in which splice sites are first paired across exons, with subsequent spliceosome assembly proceeding through pairing of exon units. In the alternative "intron definition" model, splice sites are initially paired across introns rather than exons. Intron definition is thought to be the predominant mode of splicing in transcripts containing short introns and long exons.